1. Field of the Invention
The invention generally relates to the chemotherapy or treatment of leishmaniasis and, more specifically, relates to the parenteral or oral administration of 8-amino-6-methoxyl lepidine derivatives as a means for the chemotherapy of leishmaniasis.
2. Description of the Prior Art
Leishmania are well known intra-cellular protozoan parasites which may give rise to serious infections in man. The organisms are transmitted by the "bite" of an infected sandfly, and invade the reticulo-endothelial system (RES). The parasites are highly successful in their ability to grow and multiply in the very tissues of the vertebrate host which are responsible for reaction to invading organisms. Expectedly, such location of Leishmania renders difficult a satisfactory approach to chemotherapy, and there is highly complex inter-play between parasites and cellular immune responses of the host. When Leishmania invade visceral aspects of the RES (spleen and liver, in particular), death is the common result of untreated infections. Consequences of leishmanial infections of muco-cutaneous tissues are considerably less severe, and cutaneous leishmaniasis is very rarely life-threatening in nature. There are considerable differences in response of various animals to leishmanial infections. A satisfactory animal model for laboratory trials has been found in Leishmania donovani infections in the golden hamster. In man, that parasite causes a visceral leishmaniasis which is usually fatal.
The L. donovani-hamster model has been used widely to assess candidate drugs for anti-leishmanial effects. Unfortunately, relatively few drugs have been found to show appreciable activity on screening, and fewer yet have merited trial in man. Pentavalent compounds of antimony have become mainstays for treatment of human leishmaniasis, despite liabilities of toxic side-effects. Of the antimonial drugs, one widely used in the clinic is the N-methyl glucamine salt of antimonic acid, frequently called meglumine antimoniate. That compound has been presently employed as a reference drug in evaluation of compounds in the L. donovani-hamster test.